title: Randomized study of asunaprevir plus pegylated interferon-α and ribavirin for previously untreated genotype 1 chronic hepatitis C.
abstract: BACKGROUND
  Asunaprevir is a selective NS3 protease inhibitor with in vitro activity against HCV genotypes 1 and 4.
  
  
  METHODS
  In this Phase IIa double-blind study, treatment-naive HCV genotype-1-infected patients in the United States and France were randomly assigned 1:1:1:1 to placebo or asunaprevir 200 mg twice daily, 600 mg twice daily or 600 mg once daily in combination with pegylated interferon (PEG-IFN)-α2a and ribavirin for 48 weeks. The primary efficacy end point was undetectable HCV RNA at weeks 4 and 12 (extended rapid virological response [eRVR]). Other end points included safety and undetectable HCV RNA at 24 weeks post-treatment (24-week sustained virological response [SVR24]).
  
  
  RESULTS
  A total of 47 patients were randomized and treated. eRVR was achieved by 75% (9/12), 75% (9/12) and 92% (11/12) of patients in the asunaprevir 200 mg twice-daily, 600 mg twice-daily and 600 mg once-daily groups, respectively, versus 0% (0/11) in the placebo group. Corresponding SVR24 rates were 83% (10/12), 83% (10/12) and 92% (11/12) in the asunaprevir groups and 46% (5/11) in the placebo group. There was no virological breakthrough in any asunaprevir group. Following the 12-week analysis, the 600 mg doses were reduced to 200 mg twice daily because of a greater frequency of transaminase elevations at the 600 mg dose. The most common grade 3-4 laboratory abnormalities were consistent with those reported for PEG-IFN and ribavirin.
  
  
  CONCLUSIONS
  Asunaprevir plus PEG-IFN and ribavirin achieved higher response rates than placebo plus PEG-IFN and ribavirin, with a tolerable adverse event profile at the 200 mg twice-daily dose. This dose is being evaluated in the Phase IIb and Phase III studies.
authors.affiliation: INSERM 954, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, Vandoeuvre les Nancy, France. jp.bronowicki@chu-nancy.fr.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thuluvath
authors.forename: Dominique
authors.initials: D
authors.lastname: Larrey
authors.forename: Claudia T
authors.initials: CT
authors.lastname: Martorell
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Rustgi
authors.forename: David W
authors.initials: DW
authors.lastname: Morris
authors.forename: Ziad
authors.initials: Z
authors.lastname: Younes
authors.forename: Michael W
authors.initials: MW
authors.lastname: Fried
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
authors.forename: Christophe
authors.initials: C
authors.lastname: Hézode
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
authors.forename: Omar
authors.initials: O
authors.lastname: Massoud
authors.forename: Gary A
authors.initials: GA
authors.lastname: Abrams
authors.forename: Vlad
authors.initials: V
authors.lastname: Ratziu
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Timothy
authors.initials: T
authors.lastname: Eley
authors.forename: Alaa
authors.initials: A
authors.lastname: Ahmad
authors.forename: David
authors.initials: D
authors.lastname: Cohen
authors.forename: Robert
authors.initials: R
authors.lastname: Hindes
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.forename: Bridget
authors.initials: B
authors.lastname: Reilly
authors.forename: Patricia
authors.initials: P
authors.lastname: Mendez
authors.forename: Eric
authors.initials: E
authors.lastname: Hughes
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D007546:Isoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D007546:Isoquinolines; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D013449:Sulfonamides; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a; C571889:asunaprevir